Project Summary Adults with type 1 diabetes (T1D) are at increased risk for cognitive impairment, accelerated brain aging, and Alzheimer?s disease and related dementias (ADRD). Glycemic factors are important mediators of adverse cognitive outcomes in T1D, with long-term exposure to elevated blood glucose being associated with increased cognitive decline and ADRD. Building upon recent advances in plasma biomarker assay development and findings of elevated CSF biomarkers for Alzheimer?s disease (AD) in middle aged adults with T1D, the current project aims to characterize the relationship between plasma AD biomarkers, glycemic factors and cognitive variability (a sensitive early marker of mild cognitive impairment and ADRD) in adults with T1D. We are responding to NOT-DK-20-009 to seek an administrative supplement to 1R01DK121240-01 (Glycemic fluctuations and cognitive status in adults with type 1 diabetes; The GluCog Study) in order to develop a secondary research focus on ADRD. We will leverage ongoing participant recruitment for GluCog, which includes detailed glycemic data and high frequency cognitive assessment, by newly collecting and banking blood samples. We will utilize the NIA-AA Research Framework: b amyloid deposition (A), pathologic tau (T) and neurodegeneration (N) to classify AD status. Specifically, in 100 adults from the GluCog study, we will investigate whether 1) plasma ATN biomarkers are associated with increased cognitive variability, and 2) whether this association is moderated by glycemic factors. We hypothesize that the relationship between ATN biomarkers and cognitive variability will be greater among individuals who also have poorer glycemic control. The long-term goal of this new research focus in ADRD is to identify potentially modifiable risk factors for cognitive decline and ADRD in individuals with T1D.